Ph.D.: Neural Science, Washington University in St. Louis

B.A.:Chemistry, Johns Hopikins University

Synaptic plasticity, the ability of synaptic transmission to be modulated up or down, over short time scales (milliseconds and seconds) and long time scales (minutes, hours, days, forever) underlies every aspect of normal and abnormal brain function. However, our understanding of the underlying mechanisms of synaptic transmission and its modulation is far from complete.

In our laboratory we study the basic mechanisms of neurotransmitter release in three different preparations. At the mouse nerve-muscle synapse (the neuromuscular junction) we use two electrode voltage clamp to record acetylcholine-activated currents in individual muscle fibers. In a neuroendocrine cell from the adrenal gland, adrenal chromaffin cells, we use perforated patch clamp to record tiny increases in cell capacitance that occur when vesicle membrane adds to the plasma membrane surface area. We also use carbon fiber amperometry to detect released norepinephrine and epinephrine from individual adrenal chromaffin cells. More recently we have added cultures of cortical neurons to our repertoire. Here we can record spontaneously occurring synaptic currents that arise from release of glutamate-containing vesicles from presynaptic terminals. Our laboratory has used these three preparations to study the function of Rab3A, a small GTPase associated with the membrane of synaptic vesicles. We have found that Rab3a plays multiple roles in neurotransmitter release, including regulating release of vesicles during repetitive stimulation, and regulating the kinetics of the single release event itself.

Currently, our laboratory is very interested in one form of synaptic plasticity that we believe affects the way the nervous system responds to injury and loss of synaptic inputs. To mimic such an injury, we block the activity of neurons for prolonged periods of time. It is well known that neurons respond to such a dramatic loss in activity with changes that attempt to bring the activity of the neurons back to normal. We are studying one aspect of this response, the increase in the amplitude of the spontaneously occurring miniature synaptic event, which corresponds to the response of a neuron to the release of a single vesicle of neurotransmitter. We find that at the neuromuscular junction, the normal increase in the miniature current amplitude after activity blockade is abolished in mice expressing a mutant form of Rab3A.

Koesters AG, Rich MM, Engisch KL. Diverging from the Norm: Reevaluating What Miniature Excitatory Postsynaptic Currents Tell Us about Homeostatic Synaptic Plasticity. Neuroscientist. 2022 Jul 29:10738584221112336. doi: 10.1177/10738584221112336. Epub ahead of print. PMID: 35904350.

 Hanes, AL, Koesters, A, Fong, M-F, Altimimi, HF, Stellwagen, D, Wenner, P, and Engisch, KL (2020) Divergent synaptic scaling of miniature EPSCs following activity blockade in dissociated   neuronal cultures. Journal of Neuroscience 40:4090-4102.

Koesters, A, Engisch, KL, Rich, MM. (2014) Decreased cardiac excitability secondary to reduction of sodium current may be a significant contributor to reduced contractility in a rat model of sepsis. Critical Care 18 (2): R54.

Rohan, JG, Citron, YR, Durrell, AC, Cheruzel, AE, Gray, HB, Grubbs, RH, Humayun, M, Engisch, KL, Pikov, V, Chow, RH. (2013) Light-triggered modulation of cellular electrical activity by ruthenium diimine nanoswitches. ACS Chemical Neuroscience 4:585-93.

Wang, X, Wang, Q, Yang, S, Bucan, M, Rich, MM, and Engisch, KL. (2011) Impaired activity-dependent plasticity of quantal amplitude at the neuromuscular junction of Rab3A deletion and Rab3A Earlybird mutant mice. Journal of Neuroscience 31:3580-3588.

Wang, X, Wang, Q, Engisch, KL, and Rich, MM. (2010) Activity-dependent regulation of the parameters p and n at the mouse neuromuscular junction in vivo. Journal of Neurophysiology 104:2352-2358.

Wang X, Thiagarajan R, Wang Q, Tewolde T, Rich MM, Engisch KL (2008) Regulation of quantal shape by Rab3A: evidence for a fusion pore-dependent mechanism. Journal of Physiology 586:3949-3962.

Wang X, Engisch KL, Teichert RW, Olivera BM, Pinter MJ, Rich MM (2006) Prolongation of evoked and spontaneous synaptic currents at the neuromuscular junction after activity blockade is caused by the upregulation of fetal acetylcholine receptors. Journal of Neuroscience26:8983-8987.

Thiagarajan R, Wilhelm J, Tewolde T, Li Y, Rich MM, Engisch KL (2005) Enhancement of asynchronous and train-evoked exocytosis in bovine adrenal chromaffin cells infected with a replication deficient adenovirus, Journal of Neurophysiology 94:3278-3291.

Wang X, Li Y, Engisch KL, Nakanishi ST, Dodson SE, Miller GW, Cope TC, Pinter MJ, Rich MM (2005) Activity-dependent presynaptic regulation of quantal size at the mammalian neuromuscular junction in vivo. Journal of Neuroscience 25:343-351.

Wang X, Engisch KL, Li Y, Pinter MJ, Cope TC, Rich MM (2004) Decreased synaptic activity shifts the calcium dependence of release at the mammalian neuromuscular junction in vivo. Journal of Neuroscience 24:10687-10692.

Thiagarajan R, Tewolde T, Li Y, Becker PL, Rich MM, Engisch KL (2004) Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine adrenal chromaffin cells. Journal of Physiology 555:439-457.

Engisch KL, Rich MM, Cook N, Nowycky MC (1999a) Lambert-Eaton antibodies inhibit Ca2+ currents but paradoxically increase exocytosis during stimulus trains in bovine adrenal chromaffin Cells. Journal of Neuroscience 19:3384-3395.

Engisch KL, Rich MM, Cook N, Nowycky MC (1999b) Lambert-Eaton antibodies promote activity-dependent enhancement of exocytosis in bovine adrenal chromaffin cells. Annals of the New York Academy of Sciences868:213-216.

Engisch KL, Nowycky MC (1998) Compensatory and excess retrieval: two types of endocytosis following single step depolarizations in bovine adrenal chromaffin cells. Journal of Physiology (London) 506:608.

Engisch KL, Chernevskaya NI, Nowycky MC (1997) Short-term changes in the Ca2+ exocytosis relationship during repetitive pulse protocols in bovine adrenal chromaffin cells. Journal of Neuroscience 17:9020-9025.

Engisch KL, Nowycky MC (1996) Calcium dependence of large dense-cored vesicle exocytosis evoked by calcium influx in bovine adrenal chromaffin cells. Journal of Neuroscience 16:1359-01369.

Engisch KL, Wagner JJ, Alger BE (1996) Whole-cell voltage-clamp investigation of the role of PKC in muscarinic inhibition of IAHP in rat CA1 hippocampal neurons. Hippocampus 6:183-191.